Universal Use of EFV-TDF-FTC and AZT-3TC-LPV/r Combinations for HIV-1 PMTCT in Pregnant and Breastfeeding Women : a Phase 3 Trial (UMA)
Safety and Efficacy of the Universal Use of EFV-TDF-FTC and AZT-3TC-LPV/r Combinations in Pregnant and Breastfeeding Women to Prevent mother-to Child Transmission of HIV-1 o, Resource-limited Settings: A Multicentre Randomized Phase 3 Clinical Trial
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
The prevention of MTCT during pregnancy and through breastfeeding exposure remains challenging to date in most resource-limited settings. Peripartum HIV transmission is already amenable to ARV interventions. These ARV regimens, partially efficacious are insufficiently used despite their apparent simplicity. The postnatal transmission via breastfeeding remains a serious additional threat.
This is a multicentric, non-inferiority, randomized controlled trial aiming at assessing the maternal and infant safety of a single daily fixed-dose combination of TDF/FTC/EFV (Atripla®), compared to the association of LPV/r (Kaletra® or Aluvia®) and 3TC/ZDV (Combivir®) given to African women (in Cote d'Ivoire an in Zambia) to prevent MTCT overall in breastfeeding population.
The fixed-dose combination of Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV or Atripla®) is a highly effective HAART combination and the simplest ARV regimen currently available in resource-limited settings and is therefore likely to become soon the lead first-line HAART regimen for adults in such settings. Its anticipated widespread prescription in women of childbearing age requires the proper documentation of its use in pregnancy and during breastfeeding.
The combination of ZDV/3TC (Combivir®) and Lopinavir/ritonavir (LPV/r) (Kaletra® or Aluvia®) is chosen as a reference regimen as it is one of the most commonly used first-line HAART for adults and the reference regimen for PMTCT in industrialised settings.
The maternal ARV regimen will be initiated as soon as possible from 20 weeks of gestation until at least the cessation of breastfeeding (with the advice to cease at six months). The decision to stop or continue the maternal ARV regimen after breastfeeding cessation will be based on the baseline maternal CD4 count and the maternal clinical stage at baseline and/or at breastfeeding cessation. A woman with a baseline CD4 <500 cells/ml will always be proposed to continue her treatment after breastfeeding cessation. A woman with a baseline CD4 count >500 will be asked to stop her treatment after breastfeeding cessation unless she has reached the WHO clinical stage IV at that time.
Infants will receive daily Zidovudine syrup from birth during the first week of life, or an updated ARV post-exposure prophylaxis recommended by WHO when women receive HAART.
Tipo de estudo
Estágio
- Fase 3
Contactos e Locais
Locais de estudo
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Abidjan, Costa do Marfim
- Programme PAC-CI, site ANRS
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Lusaka, Zâmbia
- Center for Infectious Desease Reserach in Zambia
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- being pregnant, presenting in at least the 20th week of pregnancy and no later than 2 weeks before the expected term;
- at least 18 years of age;
- diagnosed as infected with HIV-1 only;
- not currently taking any ARV drugs;
- having not been exposed to NVP in the 6 months preceding enrolment;
- willing to breastfeed their forthcoming child;
- residing and planning to continue to reside within the predefined catchment areas until 12 months after delivery;
- being able to give informed consent for enrolment in the study;
- lacking any medical contraindication to any of the proposed ARV medications;
- and accepting the principle of being randomized to receive one of the ARV regimens evaluated within the study, to prevent MTCT and for their own health when required.
Exclusion Criteria:
- presenting within 2 weeks before the expected term;
- currently taking ARV drugs;
- having been exposed to NVP in the 6 months preceding enrolment;
- not willing to breastfeed their forthcoming child;
- having severe renal insufficiency (creatin clearance < 60ml/min);
- diagnosed as infected with HIV-2 only or dually infected HIV-1 and HIV-2;
- hemoglobin < 7 g/dL in the month preceding inclusion
- HBs Ag positive
Women meeting one of the three last exclusion criteria (HIV-2 infection or co-infection, hemoglobin < 7 g/dL, HBs Ag positive) will not be randomized but will all received Atripla and be followed-up in an ancillary open cohort according the same procedures and agenda.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador Ativo: Atripla (R)
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Atripla (R) : Efavirenz 600 mg - Tenofovir 300 mg - Emtricitabine 200 mg; Dosage : 1 pill/day
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Comparador Ativo: Combivir (R) + Kaletra (R) or Aluvia (R)
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Combivir (R) : Zidovudine 300 mg - Lamivudine 150 mg Dosage : 1 pill twice a day Kaletra (R) or Aluvia (R) : Lopinavir 200 mg / Ritonavir 50 mg Dosage : 2 or 3 pills twice a day |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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cumulative occurence of : -adverse pregnancy outcomes (spontaneous abortion, stillbirth, congenital abnormality requiring surgical correction in children < 1 yr of age); -paediatric HIV infection; -infant mortality
Prazo: at 6 and 12 months following delivery/birth
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at 6 and 12 months following delivery/birth
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Medidas de resultados secundários
Medida de resultado |
Prazo |
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occurence of grade 4 events in treated women, and of grade 3 or 4 events in ARV-exposed infants
Prazo: at 6 and 12 months following delivery/birth
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at 6 and 12 months following delivery/birth
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frequency of virological failure (>300 copies/mL) and viral resistance profile
Prazo: at 6 month and 12 months post-delivery
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at 6 month and 12 months post-delivery
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frequency of premature delivery (<37 weeks) and frequency of low birth weight (<2500 g)
Prazo: at delivery/birth
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at delivery/birth
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cumulative incidence of paediatric HIV infection
Prazo: at 12 months after delivery
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at 12 months after delivery
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tolerability of the ARV combination in treated women
Prazo: at 6 and 12 months following delivery/birth
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at 6 and 12 months following delivery/birth
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Colaboradores e Investigadores
Investigadores
- Cadeira de estudo: Didier K Ekouevi, MD, PhD, Programme PACCI Abidjan, Cote d'Ivoire
- Cadeira de estudo: François Dabis, MD, PhD, Bordeaux 2 University, France
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Antecipado)
Conclusão do estudo (Antecipado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Processos Patológicos
- Infecções por vírus de RNA
- Doenças Virais
- Infecções transmitidas pelo sangue
- Doenças Sexualmente Transmissíveis, Virais
- Doenças Sexualmente Transmissíveis
- Infecções por Lentivírus
- Infecções por Retroviridae
- Síndromes de Deficiência Imunológica
- Doenças do sistema imunológico
- Atributos da doença
- Doenças de Vírus Lento
- Infecções por HIV
- Infecções
- Doenças Transmissíveis
- Síndrome da Imunodeficiência Adquirida
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Antivirais
- Inibidores da transcriptase reversa
- Inibidores da Síntese de Ácido Nucleico
- Inibidores Enzimáticos
- Agentes anti-HIV
- Antirretrovirais
- Antimetabólitos
- Inibidores de Protease
- Inibidores do citocromo P-450 CYP3A
- Inibidores da enzima citocromo P-450
- Indutores Enzimáticos do Citocromo P-450
- Indutores de citocromo P-450 CYP3A
- Inibidores da Protease do HIV
- Inibidores de Protease Viral
- Indutores do Citocromo P-450 CYP2B6
- Inibidores do citocromo P-450 CYP2C9
- Inibidores do citocromo P-450 CYP2C19
- Tenofovir
- Emtricitabina
- Ritonavir
- Lopinavir
- Lamivudina
- Zidovudina
- Efavirenz
- Lamivudina, combinação de drogas zidovudina
Outros números de identificação do estudo
- ANRS 12200 UMA
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